Magnetic nanoparticles (MNPs) are useful for many biomedical applications including magnetic resonance imaging (MRI) contrast agents, hyperthermia therapies, targeted drug delivery, magnetic separation, and biosensors. Significant advances have recently been made in the synthesis of MNPs with defined composition, size, shape, and magnetic properties. Among the methodologies known in the art for preparing MNPs, high-temperature thermal decomposition of organometallic precursors in nonpolar solvents has been widely shown to be capable of producing MNPs with narrow size distribution, low crystalline defects, and tunable shapes. Currently, most biomedical applications of MNPs are focused on the use of superparamagnetic nanoparticles (SPMNPs), which are MNPs with a magnetic dipole moment that flip randomly at room temperature. In contrast to SPMNPs, ferrimagnetic and ferromagnetic nanoparticles (FMNPs) have a permanent magnetic dipole moment at a given temperature in the absence of an applied magnetic field. The stability of FMNPs at room temperature make FMNPs promising candidates for biomolecular detection and imaging; however, unlike SPMNPs, FMNPs have the disadvantage of being subject to strong magnetic attractive interactions between the nanoparticles, which results in particle aggregation. As a result of this magnetically-induced particle aggregation, it is difficult to form high quality dispersions of FMNPs in physiological media for biomedical applications.
The effective use of FMNPs for a given biomedical application requires modifying the nanoparticle surface to: (1) improve colloidal stability in high ionic strength buffer solution; and (2) provide the surface functionality for further conjugation with biomolecules. The surface modification of FMNPs with a nonmagnetic polymer shell represents a viable route to improve the colloidal stability of FMNPs in a variety of solvents, as well as provide surface functionalities for interfacing with biological molecules. There are two primary approaches used in the formation of core-shell FMNP-polymer complexes (FMNP@polymer): (1) preformation of a polymeric template followed by nucleation and growth of FMNPs within the polymer matrix; and (2) pre-formation of the FMNP core followed by its surface modification with polymeric layers. The latter method is preferred for applications that require more rigorous uniformity of the particle shape, size, and composition.
The solution phase synthesis of ferrimagnetic CoFe2O4 nanoparticles with uniform size and morphology has progressed significantly in the last decade. One of the most commonly used solution phase methods for synthesizing CoFe2O4 is the thermal decomposition of Fe(acac)3 and Co(acac)2 precursors in the presence of oleic acid surfactants in a high boiling point solvent, such as benzyl ether. With this method, oleic acid surfactants protect the resulting CoFe2O4 nanoparticles and afford the nanoparticles solubility in nonpolar solvents, such as hexane. The magnetic properties of CoFe2O4 nanoparticles synthesized in this way may be changed from superparamagnetic to ferrimagnetic at room temperature by increasing the volume of the nanoparticles.
The successful synthesis of magnetic nanoparticles by the oleic acid surfactant method, however, does not ensure the successful industrial application of the nanoparticles. A disadvantage of oleic acid surfactant magnetic nanoparticle synthesis is the instability of the resulting magnetic nanoparticles, especially in the presence of FMNPs, wherein strong interparticle magnetic forces cause irreversible aggregation of the nanoparticles.